Structural Features of the Interleukin-10 Family of Cytokines

Zdanov, Alexander

doi:10.2174/1381612043382602

Cited by 57 publications

(48 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another interesting result was that IL-26 did not induce any observable biological activities in the RHE system, although it was able to induce Stat3 activation in the Colo205 cell line as previously reported (29). The reason for this lack of activity in our system is unclear but may have to do with structural properties of IL-26 that it does not share with the other IL-20 subfamily members, such as its ability to bind cell surface proteoglycans and the possibility of IL-26 forming dimers in solution (65). Colon cell lines and intestinal tissues express the IL-20R1 chain at relatively high levels, and IL-26 is the only IL-20 subfamily cytokine that binds this subunit with high affinity (28,29).…”

Section: Discussionmentioning

confidence: 94%

The Effects of IL-20 Subfamily Cytokines on Reconstituted Human Epidermis Suggest Potential Roles in Cutaneous Innate Defense and Pathogenic Adaptive Immunity in Psoriasis

Susan

Valdez²,

Wu³

et al. 2007

The Journal of Immunology

446

256

View full text Add to dashboard Cite

IL-19, IL-20, IL-22, IL-24, and IL-26 are members of the IL-10 family of cytokines that have been shown to be up-regulated in psoriatic skin. Contrary to IL-10, these cytokines signal using receptor complex R1 subunits that are preferentially expressed on cells of epithelial origin; thus, we henceforth refer to them as the IL-20 subfamily cytokines. In this study, we show that primary human keratinocytes (KCs) express receptors for these cytokines and that IL-19, IL-20, IL-22, and IL-24 induce acanthosis in reconstituted human epidermis (RHE) in a dose-dependent manner. These cytokines also induce expression of the psoriasisassociated protein S100A7 and keratin 16 in RHE and cause persistent activation of Stat3 with nuclear localization. IL-22 had the most pronounced effects on KC proliferation and on the differentiation of KCs in RHE, inducing a decrease in the granular cell layer (hypogranulosis). Furthermore, gene expression analysis performed on cultured RHE treated with these cytokines showed that IL-19, IL-20, IL-22, and IL-24 regulate many of these same genes to variable degrees, inducing a gene expression profile consistent with inflammatory responses, wound healing re-epithelialization, and altered differentiation. Many of these genes have also been found to be up-regulated in psoriatic skin, including several chemokines, ␤-defensins, S100 family proteins, and kallikreins. These results confirm that IL-20 subfamily cytokines are important regulators of epidermal KC biology with potentially pivotal roles in the immunopathology of psoriasis.

show abstract

Section: Discussionmentioning

confidence: 94%

The Effects of IL-20 Subfamily Cytokines on Reconstituted Human Epidermis Suggest Potential Roles in Cutaneous Innate Defense and Pathogenic Adaptive Immunity in Psoriasis

Susan

Valdez²,

Wu³

et al. 2007

The Journal of Immunology

446

256

View full text Add to dashboard Cite

show abstract

“…The IL-10 family IL-10 cytokine family members (IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29) are mainly linked through their similar intron-exon structure [73] . IL-10: IL-10 (OMIM 124092) is an anti-inflammatory cytokine produced by B cells, T cells, NK cells, monocytes, macrophages, and dendritic cells (DCs).…”

Section: Il-15: Il-15 (Omim 600554mentioning

confidence: 99%

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

Magyari

Várszegi

Kövesdi

et al. 2014

WJO

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologic targets for RA treatment. The identification of diseaseassociated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual's genetics.

show abstract

“…Although the quality of this homology model requires further experimental consideration, it does predict that Lys-77 and Asp-194 can form a highly conserved salt bridge joining helices A and F. The function of this salt bridge in the IL-19 subfamily is not well understood; however, it is highly characteristic of this class of ␣-helical interleukins (e.g. IL-10, IL-19, IL-20, and IL-22) (27). Our homology model of IL-24 also predicts that two of the N-linked glycosylation sites (sites I and III) localize to loops at the "top" of the molecule, whereas an additional site (site II) localizes to a loop at the base of helix B.…”

Section: Conservation Of N-glycosylation Sequons-mentioning

confidence: 99%

Structural Mapping of Post-translational Modifications in Human Interleukin-24

Fuson

Zheng

Craxton

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Human interleukin-24 (IL-24) is unique among the IL-10 superfamily as there is considerable evidence that it possesses multiple anti-cancer properties, including direct tumor cell cytotoxicity, helper T cell (TH1) immune stimulation, and anti-angiogenic activities. The primary sequence of human IL-24 differs from homologous cytokines, because it possesses three consensus N-linked glycosylation sites and the potential for a single disulfide bond. To address the significance of these modifications in human IL-24, we analyzed the relationship between post-translational modifications and the cytokine activity of the human IL-24 protein. In contrast to related interleukins, we identified a relationship between net glycosylation, protein solubility, and cytokine activity. In addition, abrogation of the two cysteine residues by mutagenesis dramatically altered the ability of IL-24 to secrete from host cells and resulted in the concomitant loss of IL-24 activity. We conclude that, unlike other IL-10 family members, human IL-24 must be glycosylated to maintain solubility and bioavailability. Further, a single, unique disulfide bond is required for secretion and activity. These structure-function relationships show that, although IL-24 is a member of the IL-19 subfamily of IL-10-like cytokines by sequence similarity, its surface properties and its distinctive disulfide arrangement make it unique. These observations could explain the novel biological activities measured of this cytokine. Understanding the structural basis of IL-24 activity will be important in the interpretation of the function of this cytokine and in the development of scale-up strategies for biophysical and clinical applications.

show abstract

Structural Features of the Interleukin-10 Family of Cytokines

Abstract: Abstract:The interleukin-10 (IL-10) family of cytokines includes IL-10, a number of its viral gene homologs, and eight recently discovered cellular cytokines

Cited by 57 publications

References 85 publications

The Effects of IL-20 Subfamily Cytokines on Reconstituted Human Epidermis Suggest Potential Roles in Cutaneous Innate Defense and Pathogenic Adaptive Immunity in Psoriasis

The Effects of IL-20 Subfamily Cytokines on Reconstituted Human Epidermis Suggest Potential Roles in Cutaneous Innate Defense and Pathogenic Adaptive Immunity in Psoriasis

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

Structural Mapping of Post-translational Modifications in Human Interleukin-24

Contact Info

Product

Resources

About